1. Field of the Invention
The present invention relates to an antibacterial agent effective against Mycobacterium avium subsp. paratuberculosis, and to a therapeutic agent for Johne's disease containing the antibacterial agent.
2. Description of the Related Art
Johne's disease is a contagious disease that affects cattle, sheep and other ruminants. The disease is caused by Mycobacterium avium subsp. paratuberculosis, an acid-fast bacillus, and is orally transmitted from one animal to another. Among major symptoms of the disease are chronic enteritis and a significant reduction in body weight. In Japan, Johne's disease was designated as a legal communicable disease in 1971. The disease has an extremely long course and may remain latent for one to several years, in some cases for as long as 10 years, before it develops. Asymptomatically-infected cattle excrete a large number of bacteria in their feces that can infect other animals in the herd (See, C. Cocito, P. Gilot, M. Coene, M. de Kesel, P. Poupart, and P. Vannuffel; Paratuberculosis; Clinical Microbiology Reviews, vol. 7, No. 3, pp 328-345 (1994)).
One approach to counteract Johne's disease is vaccination by subcutaneous injection of inactivated Johne's disease bacteria with an oil adjuvant (van Schaik G, Kalis C H, Benedictus G, Dijkhuizen A A, Huirne R B, Cost-benefit analysis of vaccination against paratuberculosis in dairy cattle. Vet Rec 139: 624-7 (1996), and Molina J M, Anguiano A, Ferrer O, Study on immune response of goats vaccinated with a live strain of Mycobacterium paratuberculosis. Comp Immunol Microbiol Infect Dis 19: 9-15 (1996)). Although vaccination can enhance the cellular immunity after infection, it only suppresses the onset of the disease, rather than prevent infection, resulting in latently infected cattle that continuously excrete bacteria in their feces. Thus, vaccination may not provide a decisive solution, but rather may spread the disease.
With no effective measures presently available for the prevention or treatment of the disease, the most effective way to prevent epidemic is to quickly find and eliminate infected animals. The Act on Domestic Animal Infectious Disease Control in Japan requires that the infected animals be disposed of immediately. Johne's disease can affect a large population of animals and is considered one of the most important diseases that can severely damage the cattle dairy and husbandary industry. The disease can not only cause direct damage to the industry by decreasing the productivity and requiring disposal of affected animals, but can also lead to a significantly increased cost associated with long-term, regular health check-ups and restricted translocation of affected animals.
At present, no effective antibacterial agents against Mycobacterium avium subsp. paratuberculosis are available, nor are there any therapeutic agents containing such antibacterial agents.